Molecular Evidence Of The Independent Origin Of Multiple Wilms Tumors In A Case Of WAGR Syndrome

Main Category: Cancer / Oncology
Also Included In: Pediatrics / Children's Health
Article Date: 13 Jul 2008 - 0:00 PDT

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UroToday.com - A study by Dr. Uccini, et al., evaluated the molecular evidence of the independent origin of multiple Wilms tumors in a patient who has WAGR syndrome. The paper was a description of the procedure, technique and its results. They had one patient who was 1 year of age. This child developed two synchronous bilateral Wilms tumors that were resected by partial nephrectomy. Histologically, these tumors were fetal rhabdomyomatous nephroblastomas. Immunohistochemical study revealed the absence of nuclear expression of WT1 protein, while beta catenin protein was expressed at nuclear level by the large majority of tumor cells present. Further investigations showed that the WT1 gene and exon 3 of beta-catenin gene had no mutations.

When this patient was 4 years of age, which was 28 months after the chemotherapy completion from the first Wilms tumor, a third Wilms tumor developed in the left kidney. The tumor was surgically removed prior to any further chemotherapy. Nine months after surgery, a metastasis was detected in the left lung. Both the third renal tumor and the lung metastasis showed a blastema-predominant morphology. Immunohistochemistry confirmed the lack of expression of WT1 protein, while beta catenin protein was expressed at nuclear level by a large majority of tumor cells. The molecular analysis of this third renal tumor and the lung metastasis revealed a 4 bp deletion in exon 7 of WT1 gene. This then led to a frameshift of the reading frame and to a premature stop of the translation. No mutations in the exon 3 of the beta-catenin gene were documented.

From this analysis, the group concluded their data supports the theory that multiple Wilms tumors can arise as a consequence of different genetic events in a single patient who has a genetic predisposition to Wilms tumor. The truly interesting question is why this mutation occurs. Was it due to the gene altering itself secondarily to chemotherapy or just that it truly is a process of the WAGR syndrome?

Uccini S, Perotti D, Colarossi C, Stoppacciaro A, Sardella M, Mannarino O, Collini P, Casieri P, Cozzi D, Amoroso L, Spreafico F, Radice P, Dominici C.
Pediatr Blood Cancer. 2008 Feb 21.

Written by UroToday.com Medical Editor Pasquale Casale, MD

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